Denosumab produces a continuous increase in bone mineral density over ten years, associated with a low risk of vertebral and non-vertebral fractures. Denosumab is well tolerated and easy to manage in daily clinical practice. For all these reasons, this treatment has a huge success. On the other hand, discontinuation of treatment is associated with a severe rebound effect including a sharp increase in bone turnover markers, loss of the bone density gained and a risk of nearly 20% of multiple vertebral fractures in postmenopausal women. High doses of potent bisphosphonates are needed to maintain bone turnover markers in the low range of premenopausal women, to mitigate this rebound effect. Prolonged treatment with denosumab is associated with a greater rebound effect and increases the risk of an early rebound effect. The occurrence of rare side effects such as osteonecrosis of the jaw or atypical femoral fracture, as well as the onset of severe renal failure, leave clinicians at a therapeutic impasse. Continuing denosumab or switching to bisphosphonates remains suboptimal and, currently, no evidence clarifies the optimal treatment approach for these patients. The aim of this review is to give a very practical clinical approach to the use of denosumab (duration of treatment), and to the management of rebound effect and possible adverse effects.